The present invention relates to a method for preventing coloration of cefmenoxime or a salt thereof (hereinafter referred to as subject compound) in an aqueous solution or suspension.
Cefmenoxime hemi-hydrochloride, which is a representative subject compound of the present invention, has the following structural formula: ##STR1##
The subject compound of the present invention has a broad antibacterial spectrum encompassing gram-positive and gram-negative aerobic and anaerobic bacteria, is stable against various .beta.-lactamases, and displays high antibacterial activity against .beta.-lactamase producing strains. In view of these properties of the subject compound, there is a standing demand for topical preparations of the subject compound which may be used in ophthalmological, otological and rhinological fields.
When an aqueous solution of the subject compound is allowed to stand, it is markedly colorized quickly and it is the state of the art that in the absence of an effective means for preventing this coloration, there is no clinically useful liquid preparation of the subject compound.
It has thus been difficult to produce an aqueous preparation that is stable enough to permit administration as ear-drops, eye-drops or nasal drops.
Under the circumstances, the present inventor sought for a way of preventing coloration of liquid preparations of the subject compound for the purpose of developing stable aqueous preparations of the subject compound. First, a large number of compounds which have been commonly used as stabilizers or coloration inhibitors for various unstable drugs were explored for their utility in the prevention of coloration of cefmenoxime in aqueous solution. It was, however, found that they were either not effective at all in the prevention of coloration of cefmenoxime or rather tended to accelerate the coloration.